Field of the Disclosed Subject Matter
The disclosed subject matter relates to a system and method for high-throughput assessment of cellular cardiotoxicity, drug screening, and cardiogenic factors via online physiological measurements. Particularly, the presently disclosed subject matter relates to a microelectrode array that reduces signal noise and isolates signal acquisition from transmission and processing noise, an optically transparent platform for cell culture that allows for simultaneous electrical and optical data acquisition, and a method of microelectrode array fabrication that enables control of patterned cells and their respective patterned electrodes.
Background
The average cost of bringing a new drug to market is $1.3 billion dollars. It has been estimated that to end up with one drug in the market, it is necessary to screen about five to ten thousand compounds, which are then whittled away through preclinical and clinical testing for safety and efficacy to treat a particular disease. Most compounds are abandoned before testing in man, and only the best, most active and most likely not to cause harm move into the clinical phase of drug development as the lead compound, although one or two other compounds may be developed in parallel as a back-up compound.
As a compound goes through clinical trials the probability that it will eventually gain approval for marketing is quite low. In 2011, the latest probabilities of success relating to the start of a clinical phase in a drug's development, were:
Clinical Trial PhaseProbability of SuccessPhase 163%Phase 233%Phase 355%Approval80%
Most failures occur by the end of Phase 2 clinical studies, after pharmaceutical companies already invested millions of dollars in a lead drug development compound. Sometimes the back-up compound can be slotted into the development plan, but sometimes it cannot. Accordingly, the high failure rates associated with pharmaceutical development mandate careful decision making during drug development as essential to avoid costly failures.
Cardiotoxicity is a major source of costly, dangerous, late-stage drug failure. Prior methods and systems for evaluating cardiotoxicity of potential drug compounds have been expensive, time-consuming and inaccurate. Such prior methods include conventional microscopy techniques as well as computer based simulation. There is a need for an efficient and economic method and system for screening of potential drug compounds for safety issues such as cardiotoxicity and others, early in the drug development process.